Alkyl phenylpiperazinylalkylcarbamates



United States Patent 3,352,865 ALKYL PHENYLPHPERAZINYL- ALKYLCARBAMATES John J. Lalferty, Levittown, and Charles L. Zirklc, Eerwyn, Pa., assignors to Smith Kline & French Laboratories, Philadelphia, Pa., a corporation of Pennsylvania No Drawing. Filed Oct. 4, 1966, Ser. No. 584,098 5 Claims. (Cl. 260268) ABSTRACT OF THE DISCLOSURE Alkyl phenylpiperazinylalkylcarbamates have tranquilizing activity and are prepared by the reaction of a phenylpiperazinylalkylamine with a lower alkyl haloformate.

This invention relates to novel alkyl phenylpiperazinylalkylcarbamates having useful pharmacodynamic activity. More specifically the compounds of this invention have tranquilizing activity as measured by standard pharmacological procedures in animals. Exemplary of the activity shown by the compounds of this invention after oral administration is the increase in stimulus-producing response rate of pigeons, the block of avoidance behavior in monkeys and the decrease in fixed interval response rates of monkeys. These compounds are approximately equipotent to chlorpromazine.

The novel alkyl phenylpiperazinylalkylcarbamates of this invention may be represented by the following general structural formula:

N-A-NHO 0 OR FORMULA I in which A represents an alkylene chain, straight or branched, of from 2 to 6 carbon atoms, preferably 2 to 4 carbon atoms, and R represents lower alkyl of from 1 to 4 carbon atoms.

A preferred compound of this invention is ethyl N-[3-(4-phenyl-l-piperazinyl)-propyl]-carbamate.

The nontoxic pharmaceutically acceptable acid addition salts of the compounds of Formula I are also included within the scope of this invention. Both organic and inorganic acids can be employed to form such salts, illustrative acids being sulfuric, nitric, phosphoric, hydrochloric, citric, acetic, lactic, tartaric, pamoic, ethane-disulfonic, sulfamic, succinic, cyclohexylsulfamic, fumaric, maleic, benzoic and the like. These salts are readily prepared by methods known to the art.

The novel compounds of this invention as represented by Formula I above are prepared by the reaction of the appropriate phenylpiperazinylalkylamine With a lower alkyl haloformate, preferably a chloroformate. The reac tion is advantageously carried out in a nonreactive organic solvent such as chloroform or the like, preferably at room or ambient temperature, for periods up to 24 hours. The phenylpiperazinylalkylamine starting materials are known as described in the U8. Patent No. 2,722,529.

The point of novelty of the herein described invention is the alkyl carbamate moiety and the unobviousness of the utility of such phenylpiperazinylalkylamine derivatives as tranquilizers. Phenyl ring substituted piperazinylalkyl carbamates are generically disclosed in U.S. Patent No. 2,836,595 useful in the treatment of hypertension and in the prevention of nausea and vomiting.

The novel compounds of this invention may be administered orally or parenterally in conventional dosage forms such as tablets, capsules, injectables or the like, by incorporating the appropriate dose of a compound of 3,352,865 Patented Nov. 14, 1967 ice Formula I with carriers according to accepted pharmaceutical practices.

The foregoing is a general description of how to prepare the compounds of this invention. The following examples illustrate the preparation of specific com-pounds but should not be construed as a limitation of the scope of the invention set forth in Formula I.

EXAMPLE 1 To a solution of 19.8 g. (0.09 mole) of 1-phenyl-4- (3-aminopropyl)-piperazine in ml. of chloroform at 27 C. is added 4.9 g. (0.045 mole) of ethyl chloroformate in 50 ml. of chloroform. The mixture is stirred for one hour and allowed to stand at 27 C. for 17 hours. The solvents are removed in vacuo and the crude residue is recrystallized from methanol-water to yield ethyl N-[3- (4-phenyl-1-piperazinyl)-propyl]-carbarnate as the monohydrate, M.P. 53-54 C.

EXAMPLE 2 Employing the general procedures of Example 1, the following alkyl haloformates and phenylpiperazinylalkylamines are reacted to give the corresponding products:

Haloformate: ethyl chloroformate Amine: 1-phenyl-4-(Z-aminoethyl)-piperazine Product: ethyl N- [2- (4-phenyll-piperazinyl) -ethyl] -carbamate Haloformate: methyl chloroformate Amine: 1-phenyl-4-(4-aminobutyl)-piperazine Product: methyl N-[4-(4-phenyl-1-piperazinyl)-butyl]- carbamate Haloformate: propyl chloroformate Amine: l-phenyl-4 5 -aminopentyl) -piperazine Product: propyl N [5-4-phenyl-l-piperazinyl) pentyl]- carbamate Haloformate: ethyl chloroformate Amine: 1-phenyl-4-(Z-aminopropyl)-piperazine Product: ethyl N-[2-(4-phenyl-1-piperazinyl)-propyl]- carbamate What is claimed is:

1. A chemical compound selected from the group consisting of a free base and salts thereof with pharmaceutically acceptable acids, said free base having the formula:

References Cited UNITED STATES PATENTS 2,836,595 5/1958 Parcell 260-268 HENRY R. JILES, Primary Examiner. 

1. A CHEMICAL COMPOUND SELECTED FROM THE GROUP CONSISTING OF A FREE BASE AND SALTS THEREOF WITH PHARMACEUTICALLY ACCEPTABLE ACIDS, SAID FREE BASE HAVING THE FORMULA: 